Methods, systems, and kits for lung volume reduction

ABSTRACT

Lung volume reduction is performed in a minimally invasive manner by isolating a lung tissue segment, optionally reducing gas flow obstructions within the segment, and aspirating the segment to cause the segment to at least partially collapse. Further optionally, external pressure may be applied on the segment to assist in complete collapse. Reduction of gas flow obstructions may be achieved in a variety of ways, including over inflation of the lung, introduction of mucolytic or dilation agents, application of vibrational energy, induction of absorption atelectasis, or the like. Optionally, diagnostic procedures on the isolated lung segment may be performed, typically using the same isolation/access catheter.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The present invention relates generally to medical methods,systems, and kits. More particularly, the present invention relates tomethods and apparatus for effecting lung volume reduction by aspiratingisolated segments of lung tissue.

[0003] Chronic obstructive pulmonary disease is a significant medicalproblem affecting 16 million people or about 6% of the U.S. population.Specific diseases in this group include chronic obstructive bronchitis,asthmatic (without bronchitis), and emphysema. While a number oftherapeutic interventions are used and have been proposed, none arecompletely effective, and chronic obstructive pulmonary disease remainsthe fourth most common cause of death in the United States. Thus,improved and alternative treatments and therapies would be ofsignificant benefit.

[0004] Of particular interest to the present invention, lung function inpatients suffering from chronic obstructive pulmonary disease can beimproved by reducing the effective lung volume, typically by resectingdiseased portions of the lung. Resection of diseased portions of thelungs both promotes expansion of the non-diseased regions of the lungand decreases the portion of inhaled air which goes into the lungs butis unable to transfer oxygen to the blood. Lung reduction isconventionally performed in open chest or thoracoscopic procedures wherethe lung is resected, typically using stapling devices having integralcutting blades.

[0005] While effective in many cases, conventional lung reductionsurgery is significantly traumatic to the patient, even whenthoracoscopic procedures are employed. Such procedures often result inthe unintentional removal of healthy lung tissue, and frequently leaveperforations or other discontinuities in the lung which result in airleakage from the remaining lung. Even technically successful procedurescan cause respiratory failure, pneumonia, death, and many older orcompromised patients are not even candidates for these procedures. Forthese reasons, it would be desirable to provide improved methods,systems, and kits for performing lung volume reduction which overcome atleast some of the shortcomings noted above.

[0006] 2. Description of the Background Art

[0007] WO 99/01076 describes devices and methods for reducing the sizeof lung tissue by applying heat energy to shrink collagen in the tissue.In one embodiment, air may be removed from a bleb in the lung to reduceits size. Air passages to the bleb may then be sealed, e.g., by heating,to fix the size of the bleb. WO 98/49191 describes a plug-like devicefor placement in a lung air passage to isolate a region of lung tissue,where air is not removed from the tissue prior to plugging. WO 98/48706describes the use of surfactants in lung lavage for treating respiratorydistress syndrome.

[0008] Patents and applications relating to lung access, diagnosis, andtreatment include U.S. Pat. Nos. 5,752,921; 5,707,352; 5,682,880;5,660,175; 5,653,231; 5,645,519; 5,642,730; 5,598,840; 5,499,625;5,477,851; 5,361,753; 5,331,947; 5,309,903; 5,285,778; 5,146,916;5,143,062; 5,056,529; 4,976,710; 4,955,375; 4,961,738; 4,958,932;4,949,716; 4,896,941; 4,862,874; 4,850,371; 4,846,153; 4,819,664;4,784,133; 4,742,819; 4,716,896; 4,567,882; 4,453,545; 4,468,216;4,327,721; 4,327,720; 4,041,936; 3,913,568 3,866,599; 3,776,222;3,677,262; 3,669,098; 3,498,286; 3,322,126; WO 95/33506, and WO92/10971.

[0009] Lung volume reduction surgery is described in many publications,including Becker et al. (1998) Am. J. Respir. Crit. Care Med.157:1593-1599; Criner et al. (1998) Am. J. Respir. Crit. Care Med.157:1578-1585; Kotloff et al. (1998) Chest 113:890-895; and Ojo et al.(1997) Chest 112:1494-1500.

[0010] The use of mucolytic agents for clearing lung obstructions isdescribed in Sclafani (1999) AARC Times, January, 69-97. Use of aballoon-cuffed bronchofiberscope to reinflate a lung segment sufferingfrom refractory atelectasis is described in Harada et al. (1983) Chest84:725-728.

SUMMARY OF THE INVENTION

[0011] The present invention provides improved methods, systems, andkits for performing lung volume reduction in patients suffering fromchronic obstructive pulmonary disease or other conditions whereisolation of a lung segment or reduction of lung volume is desired. Themethods are minimally invasive with instruments being introduced throughthe mouth (endotracheally) and/or in some cases through the chest,(e.g., thoracoscopically), and rely on isolating the target lung tissuesegment from other regions of the lung. Isolation is usually achieved byintroducing an isolation/access catheter endotracheally to the airpassages of a lung. By positioning a distal end of an isolation/accesscatheter within an air passage which opens into a target lung tissuesegment, the segment may be isolated by occluding the air passage,typically by inflating an occlusion balloon or other structure on thecatheter within the air passage. The target lung tissue segment may thenbe collapsed by aspirating air (and any other gases or liquids that mayhave been introduced) from the segment, typically through a lumen in theisolation/access catheter. Optionally, the air passage may then besealed, for example by deploying a plug within the air passage. Suitableplugs include swellable collagen matrices which hydrate and expandwithin the air passage so that they fully occlude the passage. Othersealing methods include the use of tissue adhesives, such as fibringlues, cyanoacrylate, etc.; the use of occlusive balloons; the use ofself-expanding meshes, coils, and other occlusive structures; the use ofenergy-induced tissue fusion, such as radiofrequency tissue closure; andthe like.

[0012] In a first particular aspect of the methods of the presentinvention, air flow through and from the target lung tissue segment willbe enhanced prior to aspiration of the segment. It is an objective ofthe present invention to aspirate and reduce the volume of the lungtissue segment as completely as possible. In one instance, obstructionsto gas flow within the target tissue segment are reduced prior to orduring aspiration of the segment. Mucus and other obstructions withinthe target lung tissue segment (which is diseased and frequently subjectto blockages) will interfere with substantially complete aspiration ofthe segment unless removed, disrupted, or otherwise addressed. In asecond instance, where a lack of lung surfactant is a cause of theimpeded air flow, the present invention will provide for administering asuitable surfactant prior to or during aspiration of the target lungtissue segment.

[0013] In a first specific instance, the present invention reduces gasflow obstructions by inflating the lung tissue segment to a pressurehigher than normal respiratory inflation pressures. Optionally, portionsor segments of the lung adjacent to the target lung segments may bepartially deflated or under-ventilated at the same time that the targetsegment is being inflated at a higher than normal pressure. For example,airflow into adjacent lung segments can be partially blocked to lowerpressure in those segments, causing those segments to partiallycollapse. In a specific instance, a balloon can be used to partiallyblock the bronchus of the lung with the target lung tissue segment.

[0014] Usually, the isolated lung tissue segment will be inflated to apressure in the range from 60 cm H₂O to 200 cm H₂O, preferably in therange from 100 cm H₂O to 150 cm H₂O, usually during the administrationof general anesthesia (positive pressure ventilation). If a localanesthesia is being used, the pressure will usually be in the range from10 cm H₂O to 100 cm H₂O, preferably from 30 cm H₂O to 60 cm H₂O. Theduration of such “over inflation” will typically be in the range fromone second to 600 seconds, preferably being in the range from 5 secondsto 60 seconds. Such lung inflation may be repeated more than one time.For example, the lung inflation may be carried out by inflating theisolated lung tissue segment in a pulsatile fashion. Over inflation willusually be performed using the isolation/access catheter which was usedto isolate the lung tissue segment. Optionally, it would be possible toinflate regions of the lung percutaneously using a needle introducedthrough the chest, typically under thoracoscopic observation.

[0015] In a second specific instance, gas flow obstructions within thetarget lung tissue segment may be reduced by introducing an agent whichclears the obstructions and/or dilates the air passages to permit gasflow around any blockages. Exemplary agents include mucolytic agents,bronchodilators, surfactants, desiccants, solvents, necrosing agents,absorbents, and the like. Such agents may be introduced through acatheter, typically through the isolation/access catheter which has beenused to isolate the target lung tissue segment. Optionally, such agentsmay be heated, typically to a temperature in the range from 38° C. to90° C. to enhance activity.

[0016] In a third specific instance, gas flow obstructions are reducedby delivering mechanical energy to the lung segment, typically vibratoryenergy which will break down at least some of the obstructions.Typically, the vibratory energy will be ultrasonic energy, moretypically being ultrasonic energy having a frequency in the range from20 kHz to 20 MHz, usually from 20 kHz to 5 MHz. The mechanical energywill usually be delivered to the target lung tissue segment through anon-compressible fluid introduced to the segment, usually through theisolation/access catheter. It will be appreciated that air is a poortransmission and absorption material for ultrasonic and other vibratoryenergy. Thus, introducing a non-compressible fluid, such as saline,contrast medium, treatment solution (e.g., mucolytic solution,surfactant solution, etc.), or the like, will enhance transmission andabsorption of the energy throughout the target lung tissue segment. Thevibratory energy may then be applied either through a catheter which hasbeen introduced endotracheally and then into the target lung tissuesegment, or externally using a hand-held or other ultrasonic probeintended to deliver ultrasonic energy transcutaneously. Typically, thevibrational treatment will last for time in the range from 5 seconds to60 minutes, usually from 30 seconds to 30 minutes.

[0017] In a second aspect of the methods of the present invention,collapse of the target isolated lung tissue segment is enhanced byapplying external pressure to the isolated segment. The externalpressure will usually be applied through the chest, e.g.,thoracoscopically. Most simply, a needle can be introduced to a pleuralspace over the lung, typically intracostally (between adjacent ribs).The pleural space can then be insufflated, e.g., carbon dioxide or othergas inflation medium introduced to the pleural space, in order toincrease pressure on the lung and enhance collapse of the targetsegment. Simultaneously, the target segment will be aspirated so thatthe combined lowering of the internal pressure and raising of theexternal pressure work to substantially completely collapse the segment.Alternatively, the external pressure may be applied by inflating aballoon in the pleural space over the target lung tissue segment. Stillfurther optionally, the external pressure may be applied by a probewhich is engaged and pushed against at least a portion of the externalsurface of the lung overlying the target segment. Optionally, athoracoscopically or other percutaneously placed needle could be used topuncture and aspirate a portion of the lung, typically in conjunctionwith a catheter-based aspiration as described elsewhere herein. Forexample, portions of the lung which could not be collapsed using aninternal catheter could be targeted with an external needle bythoracoscopic visualization. Any puncture holes left in the lung couldthen be sealed with a suitable adhesive, such as a fibrin glue.

[0018] In a third aspect of the present invention, methods for reducinglung volume by isolating the lung tissue segment and aspirating theisolated segment are combined with diagnostic methods which permit, forexample, determination of whether the segment which has been accessedand isolated is in fact diseased and should be collapsed. The diagnosticmethods and steps may take a wide variety of forms. For example, theisolation/access catheter or other endotracheally introduced cathetermay be used to measure air flow to and from the lung tissue segment todetermine whether the air flow capabilities of that segment areimpaired. Alternatively or additionally, the isolation/access cathetermay be used to measure carbon dioxide concentrations within the targetlung tissue segment. Other parameters which may be measured includeforced expiratory volume, pressure, pressure/volume P/V curves, segmentcompliance curves, work of breathing data, perfusion scans,bronchograms, or the like.

[0019] In a still further aspect of the methods of the presentinvention, a target lung tissue segment is isolated and aspirated, wherethe segment is collapsed to a volume which is no greater than 40% of itsinflated size prior to aspiration, usually being no greater than 30%,and preferably being no greater than 20%. The inflated size is itsmaximum size at normal spontaneous respiratory pressures, assumed to be40 cm H₂O for patients undergoing positive pressure ventilation, thespontaneous respiratory pressure is assumed to be 90 cm H₂O. The changein volume may be determined by conventional techniques, such asthoracoscopy (X-ray), CT scans, MRI, ultrasound imaging, bronchograms,and the like.

[0020] Such efficient collapsing of the target lung tissue segment maybe achieved in any of the ways discussed above. Additionally, it may beachieved by inducing absorption atelectasis prior to aspiration. Mostsimply, absorption atelectasis can be induced by insufflating theisolated lung tissue segment with high oxygen concentrations prior toaspiration. The oxygen concentrations in the insufflation gas should beat least 50% by volume, preferably 75% by volume, and more preferablybeing substantially pure oxygen.

[0021] The present invention further provides systems for performingintraluminal lung volume reduction procedures according to the methodsof the present invention. The systems comprise at least an isolation oraccess catheter having a proximal end, a distal end, an occlusionelement near the distal end, and at least one lumen therethrough. Theisolation/access catheters are used for establishing access andisolation of a target lung tissue segment, typically by endotrachealintroduction into the air passages of the lung. In a first systemaccording to the present invention, the isolation/access catheter iscombined with a sealing catheter which carries a closure element. Asealing catheter is adapted to be introduced through the lumen of theisolation/access catheter, and the closure element is adapted to bedeployed from the isolation/access catheter within an air passageleading to the target tissue segment. The closure element typicallycomprises a swellable plug, such as a partially hydrated collagen plug.Deployment within the air passage thus permits the plug to swell in situand completely block the air passage leading into the target tissuesegment so that, once the segment is collapsed, air will not enter toreinflate the segment. Surprisingly, it has been found that suchocclusion will substantially inhibit reinflation of the lung, and thatthere is little significant collateral air flow into the collapsedregion.

[0022] In a second aspect, the systems of the present invention willcombine the isolation/access catheter with a reagent capable of eitherclearing, dilating, or widening the air passages in order to facilitatesubstantially complete aspiration of the target tissue segments.Exemplary reagents have been set forth above.

[0023] In a third aspect, the systems of the present invention willcombine the isolation/access catheter with probes intended forpercutaneous introduction to apply external pressure over the lung. Theprobes may be in the form of a needle, a balloon, or a simple engagementelement intended for pressing inwardly against the lung.

[0024] The present invention still further comprises kits which includeat least an isolation/access catheter as described above. The kits willfurther comprise instructions for use according to any of the methodsset forth above. For example, the instructions for use may set forththat the isolated lung tissue segment is to be over inflated in order toreduce blockages therein. Alternatively, the instructions for use mayset forth that certain agents (as described above) are to be introducedto the segment in order to breakdown obstructive materials prior toaspiration. Still further, the kit instructions may set forth that thelung is to be externally collapsed by applying pressure or otherexternal force to a target tissue segment prior to or simultaneous withaspiration of that segment. Still further, the instructions may setforth that the volume of the target lung tissue segment is to be reducedby at least the percentages set forth above. In all cases, the kits willusually further comprise packaging, such as a pouch, tray, tube, box, orthe like for holding the kit components together with the instructionsfor use. The instructions for use may be printed on a separate sheet(commonly referred to as a package insert) and/or may be printed on thepackaging itself. Usually, the kit components which will be introducedto the patient will be sterilized and packaged in a sterile mannerwithin the kit.

BRIEF DESCRIPTION OF THE DRAWINGS

[0025]FIG. 1 is a perspective illustration of an isolation/accesscatheter useful in the methods, systems, and kits of the presentinvention.

[0026]FIG. 2 is a cross-sectional view taken along line 2 to a FIG. 1.

[0027] FIGS. 3A-3F illustrate alternative cross-sectional views of theisolation/access catheter of FIG. 1.

[0028] FIGS. 4A-4C illustrate use of the isolation/access catheter ofFIG. 1 for isolating and collapsing a target lung tissue segmentaccording the to the methods of the present invention.

[0029]FIG. 4D illustrates one protocol for over inflating a target lungtissue segment prior to aspiration according to the present invention.

[0030]FIG. 5 illustrates an optional aspect of the present inventionwhere an insufflation gas is introduced to aid in the collapse of thetarget segment from the pleural space.

[0031]FIG. 6 illustrates an alternative optional aspect of the presentinvention where an inflatable balloon is used to externally collapse aportion of a target lung tissue segment.

[0032] FIGS. 7A-7D illustrate alternative balloon designs for use inexternal collapse of the target lung tissue segment.

[0033]FIG. 8 illustrates yet another alternative optional aspect of themethods of the present invention where a probe is used to engage andcollapse a portion of a target lung tissue segment.

[0034] FIGS. 9A-9C illustrate alternative probe designs.

[0035] FIGS. 10A-10C illustrate a sealing catheter carrying a swellableclosure element which may be used in the methods, systems, and kits ofthe present invention.

[0036]FIG. 11 illustrates use of the sealing catheter of FIGS. 10A-10Cfor selectively occluding an air passage leading to a target lung tissuesegment according to the methods of the present invention.

[0037] FIGS. 12A-12C illustrate a steerable imaging guidewire which maybe used to facilitate positioning of the isolation/access catheter usedin the methods of the present invention.

[0038]FIG. 13 illustrates a kit constructed in accordance with theprinciples of the present invention.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

[0039] Lung volume reduction is performed by collapsing a target lungtissue segment, usually within sub-lobular regions of the lung whichreceive air through a single air passage, i.e., segment of the branchingbronchus which deliver to and receive air from the alveolar regions ofthe lung. Such isolated lung tissue segments are first isolated and thencollapsed by aspiration of the air (or other gases or liquids which mayhave been introduced, as discussed below) from the target lung tissuesegment. Lung tissue has a very high percentage of void volume, soremoval of internal gases can reduce the lung tissue to a smallpercentage of the volume which it has when fully inflated, i.e. inflatedat normal inspiratory pressures. The exemplary and preferred percentagesfor the volume reduction are set forth above.

[0040] In particular, the present invention provides methods andapparatus for enhancing the aspiration and collapse of the target lungtissue segment. Such methods and apparatus may involve one or more ofthe following improvements. First, various approaches may be taken toremove or lessen obstructions to gas flow within the target tissueregion. Second, methods and apparatus may be employed to apply externalpressure over the lung to enhance the collapse achieved by internalaspiration. Third, aspiration of the gases within the target tissuesegment may be enhanced by inducing absorption atelectasis prior toaspiration. Absorption atelectasis may be induced, for example, byintroducing an oxygen-rich gas to the lung tissue segment, usually atleast 50% oxygen by weight, more usually at least 75% oxygen by weight,and preferably substantially pure oxygen. Absorption atelectasis is aphenomena which occurs when an enriched oxygen mixture is inspired. Thehigh oxygen concentration causes an increase in the partial oxygenpressure which in turn causes the rate of oxygen transfer into thecapillary blood within the alveolar regions to increase greatly. Theincreased oxygen flux may increase so much that the net flow of gas intothe blood exceeds the inspired flow of gas, causing the lung unit tobecome progressively smaller. Fourth, the access methods and apparatusmay be used for performing in situ diagnosis, usually as part of thecollapse procedure. Any one of a number of lung performancecharacteristics may be measured, typically by sampling using theisolation/access catheter.

[0041] The methods of the present invention will generally rely onaccessing the target lung tissue segment using an isolation/accesscatheter adapted to be introduced endotracheally into the bronchus ofthe lung. An exemplary isolation/access catheter 10 is illustrated inFIGS. 1 and 2 and comprises a catheter body 12 having a distal end 14, aproximal end 16, an inflatable occlusion balloon 18 near its distal end,and at least one lumen therethrough. Usually, the catheter will have atleast two lumens, and catheter 10 includes both a central lumen 20 andan annular lumen 22 defined by inner body member 24 and outer bodymember 26 which is coaxially disposed about the inner body member. Theannular lumen 22 opens to port 30 on a proximal hub 32 and provides forinflation of balloon 18. The central lumen 20 opens to port 36 on hub 32and provides for multiple functions, including optional introductionover a guidewire, aspiration, introduction of secondary catheters, suchas sealing catheters described below, and the like.

[0042] The dimensions and materials of isolation/access catheter 10 areselected to permit endotracheal introduction and intraluminaladvancement through the lung bronchus, optionally over a guidewireand/or through a primary tracheal tube structure (as illustrated in FIG.4B below). Suitable materials include low and high densitypolyethylenes, polyamides, nylons, PTFE, PEEK, and the like,particularly for the inner tubular member 24. The outer member,including the occlusion balloon, can be made from elastomeric materials,such as polyurethane, low density polyethylene, polyvinylchloride,silicone rubber, latex, and the like. Optionally, portions of the outertubular member 26 proximal to the inflatable balloon can be made thickerand/or reinforced so that they do not dilate upon pressurization of theballoon. Exemplary dimensions for the isolation/access catheter 10 areset forth in the table below. ISOLATION/ACCESS CATHETER DIMENSIONSExemplary Preferred Inner Outer Inner Outer Tubular Tubular TubularTubular Member Member Member Member Outer Diameter (mm) 0.4-4   0.6-4.5  1-1.5 2-4 Wall Thickness (mm) 0.05-0.25  0.5-0.25 0.1-0.2 0.15-0.25Length (cm)  50-150 same 50-80 same Balloon Length (mm) 5-50 10-20Balloon Diameter (mm) 2-15  6-12 (inflated)

[0043] The isolation/access catheter 10 may be modified in a number ofways, some of which are illustrated in FIGS. 3A-3F. For example, insteadof a inner and outer coaxial tube construction, the catheter can be asingle extrusion having a catheter body 30 with a circular main lumen 32and a crescent-shaped inflation lumen 34, as illustrated in FIG. 3A.Alternatively, catheter body 40 may be formed as a single extrusionhaving three lumens, i.e., a primary lumen 42 for receiving a guidewire,applying aspiration, and/or delivering secondary catheters. A secondlumen 44 can be provided for inflating the occlusion balloon, and athird lumen 46 can be provided as an alternative guidewire or aspirationlumen. Catheter body 50 comprising a main tubular body 52 having anouter layer 54 fused thereover to define a lumen 56 suitable for ballooninflation as shown in FIG. 3C. A primary lumen 58 is formed within themain tubular member 52. As a slight alternative, catheter body 60 can beformed from a primary tubular member 62, and a secondary tubular member64, where the tubular members are held together by an outer member 66,such as a layer which is applied by heat shrinking. The primary tubularmember 62 provides the main lumen 68 while secondary tube 64 provides asecondary lumen 70. The secondary lumen 70 will typically be used forballoon inflation, while the primary lumen 68 can be used for all otherfunctions of the isolation/access catheter.

[0044] Optionally, the isolation/access catheter in the presentinvention can be provided with optical imaging capability. As shown inFIG. 3E, catheter body 80 can be formed to include four lumens,typically by conventional extrusion processes. Lumen 82 is suitable forpassage over a guidewire. Lumens 84 and 86 both contain light fibers 88for illumination. Lumen 90 carries an optical wave guide or image fiber92. Lumen 82 can be used for irrigation and aspiration, typically afterthe guidewire is withdrawn. Balloon inflation can be effected throughthe space remaining and lumens 84 and 86 surrounding the light fibers88. A second catheter body 100 is formed as a coaxial arrangement of anumber separate tubes. Outer tube 102 contains a separate guidewire tube104 defining lumen 106 which permits introduction over a guidewire aswell as perfusion and aspiration after the guidewire is removed. Secondinner tubular member 110 will carry an optical image fiber 112 and aplurality of light fibers 112 are passed within the remaining space 114within the outer tubular member. In both catheter constructions 80 and100, forward imaging can be effected by illuminating through the lightfibers and detecting an image through a lens at the distal end of thecatheter. The image can be displayed on conventional cathode-ray orother types of imaging screens. In particular, as described below,forward imaging permits a user to selectively place the guidewire foradvancing the catheters through a desired route through the branchingbronchus.

[0045] Referring now to FIG. 4A, a catheter 10 can be advanced to adiseased region DR within a lung L through a patient's trachea T.Advancement through the trachea T is relatively simple and willoptionally employ a guidewire to select the advancement route throughthe branching bronchus. As described above, steering can be effectedunder real time imaging using the imaging isolation/access cathetersillustrated in FIGS. 3E and 3F. Optionally, the isolation/accesscatheter 10 may be introduced through a visualizing tracheal tube, suchas that described in U.S. Pat. No. 5,285,778, licensed to the assigneeof the present application. The visualizing endotracheal tube 120includes an occlusion cuff 122 which may be inflated within the tracheajust above the branch of the left bronchus and right bronchus LB and RB,respectively. The visualizing endotracheal tube 120 includes aforward-viewing optical system, typically including both illuminationfibers and an image fiber to permit direct viewing of the main branchbetween the left bronchus LB and right bronchus RB. Thus, initialplacement of isolation/access catheter can be made under visualizationof the visualizing endotracheal tube 120 and optionally theisolation/access catheter 10 itself. Referring again in particular toFIG. 4A, the isolation/access catheter 10 is advanced until its distalend 14 reaches a region in the bronchus which leads directly into thediseased region DR. Once in place, the balloon 18 can be inflated andthe lung tissue segment which includes the diseased region isolated fromthe remainder of the lung. By isolated, it is meant that air or othergases will not pass between the isolated region and the remainingportions of the lung to any significant extent.

[0046] As shown in FIG. 4C, it is the object of the present invention toapply a vacuum to a lumen within the isolation/access catheter 10 toaspirate the internal regions within the isolated lung tissue segment inorder to collapse the tissue. This results in a collapsed lung tissueregion CLT, as shown as a shaded region in FIG. 4C.

[0047] According to the present invention, a variety of steps andprotocols may be performed prior to aspirating the isolated lung tissueregion in order to enhance gas removal from the region. The region maybe over inflated, subjected to vibrations, subjected to a dilating ormucolytic agent, or otherwise treated in order to remove gas flowobstructions within the region. Each of these methods has been welldescribed above and will generally rely on performance of at least oneaspect of the procedure using a lumen of the isolation/access catheter10. For example, over inflation can be effected simply by introducing aninflation gas through the isolation/access catheter to a desiredpressure. Pressure may be measured using a transducer at the distal tipof the catheter 10, but will usually be measured statically at alocation proximal of the catheter. Alternatively or additionally, anoxygen-rich gas can be introduced through the isolation/access catheterin order to induce absorption atelectasis. For vibratory stimulationincompressible fluid may be introduced through the isolation/accesscatheter. Stimulation may be imparted using an external probe and/or avibratory catheter which is introduced through an access lumen of theisolation/access catheter.

[0048] As shown in FIG. 4D, in some instances it will be desirable toreduce or selectively control the inflation of the lung tissue adjacentto the target lung tissue segment in order to enhance aspiration of thetarget segment. For example, an entire one-half lung can be selectivelycontrolled by an isolation or shunting catheter having a balloon 132near its distal end. The balloon is inflated to occlude a portion of theselected bronchus, typically about 60% of the area. Thus, pressurewithin the lung can be reduced and the lung partly collapsed other thanin the isolated region. In this way, inflation of the target lung tissuesegment can be enhanced which can assist in breaking up occlusionswithin the lung which would otherwise interfere with subsequentaspiration of the segment.

[0049] In addition to such in situ techniques for enhancing lungaspiration and collapse, the present invention can rely on applicationof an external force to assist in collapse. As illustrated in FIG. 5, aneedle or other cannula 200 can be percutaneously introduced into aperitoneal space PS between the parietal pleural PP and visceral pleuralVP. Insufflation gas, such as carbon dioxide, can be introduced throughthe needle 200, either using a syringe or other pressure source. The gaswill typically be introduced to a pressure in the range from 30 half cmH₂O to 200 cm H₂O in spontaneously breathing patients and 70 cm H₂O to250 cm H₂O in positive pressure ventilated patients.

[0050] Use of an unconstrained insufflation gas, however, isdisadvantageous since it is not directed at a particular targetlocation. In order to more specifically direct an external pressureagainst the lung, a balloon 210 can be introduced to the pleural space,typically through a thoracic trocar 212. The balloon can be placed basedon fluoroscopic observation. Depending on the particular area which isto be collapsed, a variety of specific balloon configurations can beemployed, as illustrated in FIGS. 7A-7D. A generally spherical balloon220 is shown attached to shaft 220 in FIG. 7A. Other configurationsinclude a winged profile (FIG. 7B), a cylindrical or spatula profile(FIG. 7C), and a convex profile (FIG. 7D). Each of these will beattached to a shaft which permits inflation after introduction into thepleural space.

[0051] As a further alternative to needle insufflation and balloonexpansion, a target lung tissue segment can be externally collapsedusing a simple probe 250, usually introduced through a thoracic trocar252, as shown in FIG. 8. A variety of probes for mechanically engagingand compressing the outer lung surface are illustrated in FIGS. 9A-9C.Optionally, a needle can be used to puncture at a desired point in thetarget tissue lung segment in order to release and/or aspirate air,usually as a supplement to a primary catheter-based aspiration. Thepuncture can then be sealed with fibrin glue or other suitable sealant.

[0052] The methods of the present invention will optionally comprisesealing or occluding the air passage leading to the collapsed tissueregion CLT. Such sealing can be performed in a variety of ways,including suturing, gluing, energy-mediated tissue adhesion, and thelike. In a preferred aspect of the present invention, a sealing catheter280 can be used to deliver a plug 282, typically at partially hydratedcollagen hydrogel, as illustrated in FIGS. 10A-10C. Usually, thecatheter will have dimensions which permit it to be introduced throughthe main access lumen of isolation/access catheter 10. The plug 282 willbe contained in the distal tip of a lumen in the catheter, and a pushrod 284 extends the length of the catheter to permit the treatingphysician to deploy the plug 282 after the tip of the catheter isproperly located, as illustrated in FIG. 11, usually while the balloonon the isolation/access catheter remains inflated and the target lungtissue remains sealed and in an aspirated, collapsed configuration. Oncedeployed within the moist environment of the lung bronchus, the plug 282will absorb water and will swell substantially, typically from 100% to1000% in order to fully occupy and plug the air passage into thecollapsed lung tissue region CLT.

[0053] Positioning of the isolation/access catheter 10 within the lungcan be performed using on-board optical imaging capability, as discussedabove. Usually, positioning of a guidewire through the branchingbronchus will be manipulated while viewing through the imagingcomponents of the isolation/access catheter. In this way, theisolation/access catheter can be “inched” along by alternately advancingthe guidewire and the isolation/access catheter. As an alternative toproviding the isolation/access catheter with imaging, positioning couldbe done solely by fluoroscopy. As a further alternative, a steerable,imaging guidewire 300 (FIGS. 12A-12C) could be used. The guidewire 300includes a deflectable tip 302 which can be deflected in a single planeusing push/pull ribbon 304. Usually, the tip will comprise a spring 306to facilitate deflection. In addition to steeribility, the guidewire 300will include an optical imaging wave guide 310 and illuminating opticalfibers 312, as best seen in cross-sectional view of FIG. 12C. Thus, theguidewire 300 can be steered through the branching bronchus to reach thetarget tissue segment using its own in situ imaging capability. Once theguidewire 300 is in place, an isolation/access catheter can beintroduced to the target lung tissue segment as well. Since theguidewire has imaging capability, the isolation/access catheter need notincorporate such imaging. This can be an advantage since it permits theaccess lumen to be made larger since the catheter need not carry anyoptical wave guides.

[0054] Referring now to FIG. 13, kits 400 according to the presentinvention comprise at least an isolation/access catheter 10 andinstructions for use IFU. Optionally, the kits may further include anyof the other system components described above, such as a balloon probe210, a sealing catheter 280, a reagent container 420 (optionallyincluding any of the dilating or mucolytic agents described above), orother components. The instructions for use IFU will set forth any of themethods as described above, and all kit components will usually bepackaged together in a pouch 450 or other conventional medical devicepackaging. Usually, those kit components, such as isolation/accesscatheter 10, which will be used in performing the procedure on thepatient will be sterilized and maintained sterilely within the kit.Optionally, separate pouches, bags, trays, or other packaging may beprovided within a larger package, where the smaller packs may be openedseparately and separately maintain the components in a sterile fashion.

[0055] While the above is a complete description of the preferredembodiments of the invention, various alternatives, modifications, andequivalents may be used. Therefore, the above description should not betaken as limiting the scope of the invention which is defined by theappended claims.

What is claimed is:
 1. A method for lung volume reduction, said methodcomprising: isolating a lung tissue segment; reducing gas flowobstructions within the segment; and aspirating the segment to cause thesegment to at least partially collapse.
 2. A method as in claim 1 ,wherein reducing gas flow obstructions comprises inflating the lungtissue segment to a pressure higher than its normal inflated pressure.3. A method as in claim 2 , further comprising deflating adjacent lungregions while the lung tissue segment is inflated.
 4. A method as inclaim 2 , wherein inflating the lung tissue segment comprisespositioning a catheter in an air passage leading into the segment,inflating a balloon on the catheter to seal the air passage, andintroducing a gas through the catheter to inflate the segment.
 5. Amethod as in claim 1 , wherein reducing gas flow obstructions comprisesintroducing an agent to the lung tissue segment, wherein the agentclears or dilates air passages within the segment.
 6. A method as inclaim 5 , wherein the agent is selected from the group consisting ofmucolytic agents, bronchodilators, surfactants, desiccants, solvents,necrosing agents, and absorbents.
 7. A method as in claim 5 , whereinintroducing the agent comprises positioning a catheter in an air passageleading to the segment and delivering the agent through the catheter tothe segment.
 8. A method as in claim 1 , wherein reducing gas flowobstructions comprises delivering mechanical energy to the lung segment.9. A method as in claim 8 , wherein the mechanical energy is vibrationalenergy.
 10. A method as in claim 8 , wherein the vibrational energy isdelivered by inflating the segment with a non-compressible fluid andultrasonically exciting the fluid to distribute ultrasonic energythroughout the segment.
 11. A method as in claim 1 , wherein isolatingthe lung tissue segment comprises positioning a catheter in an airpassage leading to the lung tissue segment and inflating a balloon onthe catheter to occlude the air passage.
 12. A method as in claim 11 ,wherein aspirating comprises drawing gas and liquids present from theisolated lung segment through a lumen in the catheter while the balloonremains inflated.
 13. A method as in claim 1 , further comprisingsealing an air passage which opens to the lung tissue segment to inhibitreinflation of the segment.
 14. A method as in claim 13 , whereinsealing comprises deploying a plug in the air passage.
 15. A method asin claim 14 , wherein the plug is swellable and absorbs water to swellwithin the air passage when deployed.
 16. A method as in claim 15 ,wherein the plug comprises a collagen hydrogel which is not fullyhydrated prior to deployment.
 17. A method for lung volume reduction,said method comprising: isolating a lung tissue segment; aspirating theisolated segment to cause the segment to collapse; and applying externalpressure to the isolated segment.
 18. A method as in claim 17 , whereinexternal pressure is applied by insufflating a pleural space over thelung.
 19. A method as in claim 18 , wherein the pleural space isinsufflated with a percutaneously placed needle.
 20. A method as inclaim 17 , wherein external pressure is applied by inflating a balloonin a pleural space over the lung.
 21. A method as in claim 17 , whereinexternal pressure is applied by engaging a percutaneously placed probeagainst an external surface of the lung.
 22. A method as in claim 17 ,wherein isolating the lung tissue segment comprises positioning acatheter in an air passage leading to the lung tissue segment andinflating a balloon on the catheter to occlude the air passage.
 23. Amethod as in claim 22 , wherein aspirating comprises drawing gas fromthe isolated lung segment through a lumen in the catheter while theballoon remains inflated.
 24. A method as in claim 17 , furthercomprising sealing an air passage which opens to the lung tissue segmentto inhibit reinflation of the segment.
 25. A method as in claim 24 ,wherein sealing comprises deploying a plug in the air passage.
 26. Amethod as in claim 25 , wherein the plug is swellable and absorbs waterto swell within the air passage when deployed.
 27. A method as in claim26 , wherein the plug comprises a collagen hydrogel which is not fullyhydrated prior to deployment.
 28. A method for lung volume reduction,said method comprising: isolating a lung tissue segment; determining adisease-related parameter within the isolated segment; aspirating theisolated segment to cause collapse if it is determined that the segmentis diseased.
 29. A method as in claim 28 , wherein determining adisease-related parameter comprises measuring air flow into the lungtissue segment.
 30. A method as in claim 28 , wherein determining adisease-related parameter comprises measuring carbon dioxideconcentration in the lung tissue segment.
 31. A method as in claim 28 ,wherein determining a disease-related parameter comprises measuringforced expiratory volume of the lung tissue segment.
 32. A method as inclaim 28 , wherein determining a disease-related parameter comprisesmeasuring pressure within the lung tissue segment.
 33. A method as inclaim 28 , wherein isolating the lung tissue segment comprisespositioning a catheter in an air passage leading to the lung tissuesegment and inflating a balloon on the catheter to occlude the airpassage.
 34. A method as in claim 33 , wherein aspirating comprisesdrawing gas from the isolated lung segment through a lumen in thecatheter while the balloon remains inflated.
 35. A method as in claim 28, further comprising sealing an air passage which opens to the lungtissue segment to inhibit reinflation of the segment.
 36. A method as inclaim 35 , wherein sealing comprises deploying a plug in the airpassage.
 37. A method as in claim 36 , wherein the plug is swellable andabsorbs water to swell within the air passage when deployed.
 38. Amethod as in claim 37 , wherein the plug comprises a collagen hydrogelwhich is not fully hydrated prior to deployment.
 39. A method for lungvolume reduction, said method comprising: isolating a lung tissuesegment; aspirating the isolated segment to cause the segment tocollapse, wherein the segment is collapsed to a volume which is nogreater than 40% of the inflated size prior to aspiration.
 40. A methodas in claim 39 , further comprising insufflating the isolated lungtissue segment with substantially pure oxygen to promote absorptionatelectasis prior to aspirating.
 41. A method as in claim 39 , whereinisolating the lung tissue segment comprises positioning a catheter in anair passage leading to the lung tissue segment and inflating a balloonon the catheter to occlude the air passage.
 42. A method as in claim 41, wherein aspirating comprises drawing gas from the isolated lungsegment through a lumen in the catheter while the balloon remainsinflated.
 43. A method as in claim 39 , further comprising sealing anair passage which opens to the lung tissue segment to inhibitreinflation of the segment.
 44. A method as in claim 43 , whereinsealing comprises deploying a plug in the air passage.
 45. A method asin claim 44 , wherein the plug is swellable and absorbs water to swellwithin the air passage when deployed.
 46. A method as in claim 45 ,wherein the plug comprises a collagen hydrogel which is not fullyhydrated prior to deployment.
 47. A system for performing intraluminallung volume reduction, said kit comprising: an isolation/access catheterhaving a proximal end, a distal end, an occlusion element near thedistal end, and at least one lumen extending therethrough; a sealingcatheter having a proximal end, a distal end, and a closure elementcarried by the isolation/access catheter; wherein the sealing cathetermay be introduced through the lumen of the isolation/access catheter andthe closure element may be deployed from the isolation/access catheter.48. A system as in claim 47 , wherein the closure element comprises aswellable plug.
 49. A system as in claim 47 , wherein theisolation/access catheter includes at least two lumens extendingtherethrough.
 50. A system as in claim 49 , wherein the isolation/accesscatheter further including a fiber optic scope and a light sourcedisposed to permit forward viewing.
 51. A system for performingintraluminal lung volume reduction, said kit comprising: anisolation/access catheter having a proximal end, a distal end, anocclusion element near the distal end, and at least one lumen extendingtherethrough; and a reagent capable of being introduced to the lungthrough the isolation/access catheter lumen, wherein said reagent willclear or widen air passages within the lung.
 52. A system as in claim 51, wherein the reagent is selected from the group consisting of mucolyticagents, bronchodilators, surfactants, desiccants, solvents, necrosingagents, and absorbents.
 53. A system as in claim 51 , wherein theisolation/access catheter includes at least two lumens extendingtherethrough.
 54. A system as in claim 53 , wherein the isolation/accesscatheter further includes a fiber optic scope and a light sourcedisposed to permit forward viewing.
 55. A system for performingintraluminal lung volume reduction, said kit comprising: anisolation/access catheter having a proximal end, a distal end, anocclusion element near the distal end, and at least one lumen extendingtherethrough; and a probe which can be percutaneously introduced into apleural region over the lung, said probe being capable of applyingexternal pressure to the lung.
 56. A system as in claim 55 , wherein theprobe has an inflatable balloon which engages a surface of the lung. 57.A system as in claim 55 , wherein the probe has a non-inflatableatraumatic end which engages a surface of the lung.
 58. A system as inclaim 55 , wherein the isolation/access catheter includes at least twolumens extending therethrough.
 59. A system as in claim 58 , wherein theisolation/access catheter further includes a fiber optic scope and alight source disposed to permit forward viewing.
 60. A kit comprising:an isolation/access catheter capable of being introduced transtracheallyinto the air passages of the lungs; and instructions to introduce theisolation/access catheter to a target region of the lungs and toaspirate an isolated tissue segment according to claim 1 .
 61. A kit asin claim 60 , further comprising a sealing catheter, wherein saidinstructions further set forth that an air passage leading to theisolated tissue segment is to be sealed using the sealing catheter afterthe region has been aspirated.
 62. A kit as in claim 60 , furthercomprising means for applying external pressure to the lung at the sametime the lung is being aspirated.
 63. A kit as in claim 60 , furthercomprising an agent which clears or widens air passages in the lungswhen introduced into the lungs prior to aspiration.
 64. A kit as inclaim 63 , wherein the agent is selected from the group consisting ofmucolytic agents, bronchodilators, surfactants, desiccants, solvents,necrosing agents, and absorbents.
 65. A kit comprising: anisolation/access catheter capable of being introduced transtracheallyinto the air passages of the lungs; and instructions to introduce theisolation/access catheter to a target region of the lungs and toaspirate an isolated tissue segment according to claim 17 .
 66. A kit asin claim 65 , further comprising a sealing catheter, wherein saidinstructions further set forth that an air passage leading to theisolated tissue segment is to be sealed using the sealing catheter afterthe region has been aspirated.
 67. A kit as in claim 65 , furthercomprising means for applying external pressure to the lung at the sametime the lung is being aspirated.
 68. A kit comprising:. anisolation/access catheter capable of being introduced transtracheallyinto the air passages of the lungs; and instructions to introduce theisolation/access catheter to a target region of the lungs and toaspirate an isolated tissue segment according to claim 28 .
 69. A kit asin claim 68 , further comprising a sealing catheter, wherein saidinstructions further set forth that an air passage leading to theisolated tissue segment is to be sealed using the sealing catheter afterthe region has been aspirated.
 70. A kit as in claim 68 , furthercomprising means for applying external pressure to the lung at the sametime the lung is being aspirated.
 71. A kit as in claim 68 , furthercomprising an agent which clears or widens air passages in the lungswhen introduced into the lungs prior to aspiration.
 72. A kit as inclaim 71 , wherein the agent is selected from the group consisting ofmucolytic agents, bronchodilators, surfactants, desiccants, solvents,necrosing agents, and absorbents.
 73. A kit comprising:. anisolation/access catheter capable of being introduced transtracheallyinto the air passages of the lungs; and instructions to introduce theisolation/access catheter to a target region of the lungs and toaspirate an isolated tissue segment according to claim 39 .
 74. A kit asin claim 73 , further comprising a sealing catheter, wherein saidinstructions further set forth that an air passage leading to theisolated tissue segment is to be sealed using the sealing catheter afterthe region has been aspirated.
 75. A kit as in claim 73 , furthercomprising means for applying external pressure to the lung at the sametime the lung is being aspirated.
 76. A kit as in claim 73 , furthercomprising an agent which clears or widens air passages in the lungswhen introduced into the lungs prior to aspiration.
 77. A kit as inclaim 76 , wherein the agent is selected from the group consisting ofmucolytic agents, bronchodilators, surfactants, desiccants, andsolvents.
 78. A method in claim 28 , wherein determining adisease-related parameter comprises measuring the compliance orpressure/volume curve of a lung tissue segment.